Nucleosides, Nucleotides & Nucleic Acids最新文献

Background: Breast cancer among women is the most frequently diagnosed cancer and the leading cause of death worldwide. There many advances in diagnosing and treating this disease, early diagnosis and treatment are still a significant challenge in the early stages. In recent years, microRNAs have attracted much attention in cancer diagnosis and treatment. However, the role of miR-146a in breast cancer is still controversial. We aimed to investigate the roles of miR-146a in apoptosis in breast cancer cells.

Methods: A microarray dataset from the GEO database was selected, and using the GEO2R tool, the gene expression profile of this dataset was extracted. Then, the target scan database was used to explore the miR-146a target genes. The link between the signaling pathways was collected. We used miR-146a mimic, which was transfected to the MCF-7 cells to investigate the miR-146a roles in the apoptosis. The expression levels of miR-146a and BAX, BCL-2, and p-21(most essential genes in the apoptosis) were quantified by qPCR and western blot analysis.

Results: Our findings indicated that doxorubicin induces miR-146a expression. In addition, overexpression of miR-146a affected MCF-7 cell viability, induced apoptosis, and led to reduced expression levels of BCL-2 and P-21, as well as increased BAX expression levels.

Conclusion: Considering the role of doxorubicin in inducing apoptosis and increasing the expression of miR-146a, it can be suggested that this miR is involved in inducing apoptosis in BC cells. In addition, miR-146a can be considered a therapeutic candidate.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), while generalized vitiligo(GV) is an autoimmune disease that causes the loss of functional melanocytes, resulting in white patches all over the body. Human Leukocyte Antigen (HLA) plays a crucial role in immune response to pathogens. Studies assessing the link between GV and COVID-19 are lacking; therefore, our current study was aimed to establish the association between GV and HLAB27 by genotyping the HLAB27 allele in 150 GV patients and 150 controls from South Gujarat population through polymerase chain reaction-sequence-specific primers (PCR-SSP) method. Additionally, we assessed the correlation of GV with COVID-19 and the influence of HLAB27 on COVID-19 development. Interestingly, our study suggested that the HLAB27 allele was prevalent in GV patients as compared to controls (52% vs 35.33%; p = 0.0051). Moreover, the occurrence of COVID-19 was significantly lower in GV patients than in controls (10% vs 32.66%; p < 0.0001). Disease activity-based analysis suggested that COVID-19 occurrence was significantly lower in active vitiligo (AV) patients as compared to stable vitiligo (SV) patients(6.87% vs 31.57%; p = 0.0045). Furthermore, COVID-19 development was significantly reduced in HLAB27 positive individuals as compared to HLAB27 negative individuals (p = 0.0025). Overall, our study suggests, for the first time, that HLAB27 allele might be a genetic risk factor for GV susceptibility, and an ongoing immune response in GV patients, more specifically in AV patients, might protect against COVID-19 infection in South Gujarat population. Additionally, our study highlighted the likely role of HLAB27 in protection against COVID-19 development.

Ulcerative colitis (UC) is a multifactorial intestinal disease with a high incidence. In recent years, there has been an urgent need for pleiotropic drugs with a clear biosafety profile. Tacrolimus (TAC) is an immunosuppressant with stronger in vivo effects and better gastrointestinal absorption and is considered a potential treatment for UC. FKBP12 is a mediator of TAC immunosuppression; however, it is unclear whether it can participate in the development of UC in combination with TAC. The purpose of this study is to preliminarily validate the function of FKBP12 by establishing dextran sulfate sodium (DSS)-induced UC model and TAC treatment. The results revealed that TAC was effective in alleviating DSS-induced UC symptoms such as body weight and disease activity index (DAI). TAC significantly protects colonic tissue and attenuates DSS-induced histomorphological changes. In addition, FKBP12 is down-regulated in the intestinal tissue of DSS-induced UC mice and in serum samples of UC patients. In conclusion, our study revealed that FKBP12 may act as a TAC receptor to have anti-inflammatory and protective effects on DSS-induced UC in mice, which will provide a new option for the treatment of UC.

Henoch-Schönlein purpura (HSP) is a common form of IgA1-mediated blood vessel inflammation affecting mainly children. Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been shown to be associated with HSP in different populations; in this study, we investigated its potential association and influence on the development of severe complications in Iranian HSP patients. Twenty-three patients diagnosed with IgAV/HSP according to the criteria of the American College of Rheumatology (ACR) with 53 age- and sex-matched control subjects were referred to us. Cases and controls were genotyped using Sanger sequencing. Based on our research data, we found an association between codon 469 K/E of the ICAM1 gene and risk of HSP. Our results revealed that KK genotype and allele K are more common in control than in the HSP group, therefore the subjects with KK genotype are protected against HSP. Our data also suggested that the genotype EE is associated with higher risk of HSP progression compared to KK genotype.

Ferroptosis has recently been shown to play a significant role in the progression of intervertebral disk degeneration (IDD), although the underlying mechanism is still unknown. The objective of this work was to use stringent bioinformatic techniques to clarify the crucial roles played by genes associated with ferroptosis in the emergence of IDD. For additional study, the microarray data pertinent to the IDD were acquired from the Gene Expression Omnibus database. The ferroptosis-related and IDD-related genes (FIDDRGs) were identified using a variety of bioinformatic techniques, which were also used to carry out function enrichment analysis, protein-protein correlation analysis, build the correlation regulatory network, and examine the potential connections between ferroptosis and immune abnormalities and inflammatory responses in IDD. A total of 16 FIDDRGs were eliminated for the further function enrichment analysis, and 10 hub FIDDRGs were chosen to build the correlation regulatory network. Hub FIDDRGs were shown to be highly associated with M2 macrophages and hub inflammatory response-related genes in IDD. When seen as a whole, our findings can give fresh perspectives on the mechanistic studies of ferroptosis in the emergence of IDD and new prospective targets for the therapeutic approaches.

The coronavirus disease 2019 (COVID-19) is a recent pandemic occurring worldwide due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, spreading mainly through large respiratory droplets or maybe through other transmission routes. The human genome has the most varied immune response genes correlated with infectious diseases. Genetic variants of mannose-binding lectin 2 (MBL2), an immunomodulatory gene, were associated with the risk, severity, and frequency of viral infections. In the present study, we hypothesized that the MBL2 gene rs1800450 variant could be associated with the development of COVID-19 disease in a Turkish population. Ninety-eight COVID-19 patients and 98 healthy, ethnically matched controls were studied. We isolated genomic DNA from whole blood and analyzed the MBL2 rs1800450 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Associations were analyzed with the SPSS 20 statistical software. We found that MBL2 rs1800450 genotype distribution was significantly different between patients and controls. The patients had a higher MBL2 rs1800450 AA genotype than the controls had (4.94% in patients vs. 3.12% in controls, p = 0.006). The subjects carrying AA genotype had a 10.83-fold increased risk for COVID-19 disease (OR = 10.83, %95 CI = 1.359-86.349). We could not detect any significant difference between the COVID-19 patients and healthy controls in allele frequencies. Our findings demonstrated that the MBL2 rs1800450 BB genotype might increase the susceptibility to COVID-19 disease in the Turkish population. We suggest further studies with a larger sample size and other ethnic populations.

Objective: It is necessary to identify appropriate clinical, biochemical, epidemiological and genetic biomarkers to elucidate the underlying mechanisms of the coronavirus disease-2019 (COVID-19) disease. The study focused on not only the link between disease severity (non-intense unit care (non-ICU) versus intensive unit care (ICU) and genetic susceptibility in COVID-19 patients but also the connection between comorbidity and genetic susceptibility affecting the severity of COVID-19.

Subject and methods: One hundred and sixty-two COVID-19 patients treated in the non-ICU and ICU in Kayseri City Hospital were included. All volunteers underwent a physical examination and biochemical evaluation. Angiotensin-converting enzyme (ACE p.T776T G > A(rs4343) and g.16471_16472delinsALU (also referred to as I/D polymorphism; rs1799752), angiotensin II receptor type-1 (AGTR1) c.*86A > C (also referred to as A1166C; rs5186), and plasminogen activator inhibitor-1 (PAI-1-844 G > A (rs2227631) polymorphisms were analysed as well.

Results: To have ACE "ID" genotype did not change the severity of the disease (OR: 0.92, 95% CI: 0.41-2.1, p = 0.84), but decreased the mortality risk 2.9-fold (OR: 2.9, 95% CI: 1.1-7.0, p = 0.03). In PAI-1-844 G > A, having the "AA" genotype in the "A" recessive model increased the risk of the diabetes mellitus (DM) 2.3-fold (OR: 2.3 95%, CI: 1.16-4.66, p = 0.018). In the "G" recessive model, to have the GG genotype increased the risk of chronic kidney disease (CKD) 4.8-fold (OR:4.8, 95% CI: 1.5-15.5, p = 0.008). "GG" genotype in the DM group had a higher fibrinogen level compared to those with the "AG" genotype (AG:4847.2 mg/L (1704.3) versus GG:6444.67 mg/L (1861.62) p = 0.019) and "AA" genotype in the CKD group had lower platelet levels and those with "GG" had higher platelet levels (AA:149 µL (18-159) versus GG: 228 µL (146-357) p = 0.022).

Conclusion: This study was shown that genetic predispositions that causes comorbidities were also likely to affect the prognosis of COVID-19.

Multiple signaling pathways have been discovered to play a role in aging and longevity, including the insulin/IGF-1 signaling system, AMPK pathway, TOR signaling, JNK pathway, and germline signaling. Mammalian serum and glucocorticoid-inducible kinase 1 (sgk-1), which has been associated with various disorders including hypertension, obesity, and tumor growth, limits survival in C. elegans by reducing DAF-16/FoxO activity while suppressing FoxO3 activity in human cell culture. C. elegans provides significant protection for a number of genes associated with human cancer. The best known of these are the lin-35/pRb (mammalian ortholog pRb) and CEP-1 (mammalian ortholog p53) genes. Therefore, in this study, we aimed to investigate the expression analyzes of sgk-1, which is overexpressed in many types of mammalian cancer, in mutant lin-35 and to demonstrate the validation of reference genes in wild-type N2 and mutant lin-35 for C. elegans-focused cancer research. To develop functional genomic studies in C. elegans, we evaluated the expression stability of five candidate reference genes (act-1, ama-1, cdc-42, pmp-3, iscu-1) by quantitative real-time PCR using five algorithms (geNorm, NormFinder, Delta Ct method, BestKeeper, RefFinder) in N2 and lin-35 worms. According to our findings, act-1 and cdc-42 were effective in accurately normalizing the levels of gene expression in N2 and lin-35. act-1 and cdc-42 also displayed the most consistent expression patterns, therefore they were utilized to standardize expression level of sgk-1. Furthermore, our results clearly showed that sgk-1 was upregulated in lin-35 worms compared to N2 worms. Our results highlight the importance of definitive validation using mostly expressed reference genes.

Recent reports showing that neo-atherosclerosis formation in stented coronary artery is characterized by the accumulation of lipid-laden macrophages within the neointima has strengthened the possibility that elevated low-density lipoprotein (LDL)-cholesterol may be a risk factor for in-stent restenosis (ISR). Protein Convertase Subtilisin/Kexin-9 (PCSK9) protein plays an important role in cholesterol metabolism by degrading of LDL receptors. The gain-of-function E670G (rs505151) mutation of the PCSK9 gene is a well-known genetic risk factor for hypercholesterolemia. This study evaluated for the first time the association of the E670G variation with the serum lipids, PCSK9 levels and concomitant diseases on the ISR risk. The study included 109 ISR, and 82 Non-ISR patients, based on the results of coronary angiography. Genotypes were determined using the real-time PCR and serum PCSK9 levels were measured by ELISA technique. The rare G allele of PCSK9 E670G (p < 0.05), hyperlipidemia (HL) (p < 0.001), and type 2 diabetes (T2DM) (p < 0.01) were associated with increased risk for ISR. In hyperlipidemic conditions, the E670G-G allele was associated with hypercholesterolemia and a higher risk of ISR (p < 0.001), while the E670G-AA genotype has been associated with a high prevalence of T2DM and hypertension. In addition, diabetic ISRs had higher serum PCSK9 levels (p < 0.05) and the E670G-AA genotype was associated with increased levels of diabetes markers. Our results indicated that the unusual effects of both G allele and AA genotype of the PCSK9 E670G variation may be involved in the risk of ISR in association with concomitant metabolic diseases.

Genes involved in lipid metabolism have been considered potential therapeutic targets in lung cancer because lipid metabolism is severely disrupted in this cancer. Monoglyceride lipase (MGLL) is a lipolytic enzyme that converts monoacylglycerides to fatty acids and glycerol. MicroRNAs (miRNA), one of the most important epigenetic regulators of gene expression, are also considered potential biomarkers in diagnosing, treating, and prognosis lung cancer. This study aimed to investigate the potential effects of MGLL and related miRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in the pathogenesis of non-small cell lung cancer (NSCLC) by examining their expression levels and regulatory mechanisms. We analysed the expression levels of MGLL and miRNAs in 30 NSCLC and 20 non-cancerous tissues by qPCR. We performed in silico analyses to determine the biological functions of MGLL and miRNAs in NSCLC. A protein-protein interaction (PPI) network was constructed for MGLL, and gene ontology (GO) analysis, and the interacting genes were analysed using the TCGAnalyzer tool. Our study showed that the expression levels of MGLL, miR-302b-5p, miR-190a-3p and miR-450a-2-3p were significantly decreased in NSCLC tissues (p < 0.05). Also, according to TCGAnalyzer, MSRB3, HTR4, and FCER1G genes were downregulated genes for NSCLC. We showed that miR-302b-5p, miR-190a-3p, and miR-450a-2-3p significantly regulate the TGF-β signalling pathway. In conclusion, this study provides evidence for the potential role of MGLL and microRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in NSCLC. In subsequent studies, it was determined that MSRB3, FCER1G and LTB4R2 genes, especially the HTR4 gene, could be potential target genes for lung cancer.